Long-term exposure to air pollution, particularly traffic-related air pollution, is associated with cardiovascular morbidity and mortality. Less is known about the impact of these exposures on neurodegenerative disorders. Evidence suggests that systemic inflammation, a response to which the brain is particularly vulnerable, may mediate cardiovascular effects, suggesting that neurodegenerative disorders may also be subject to this environmental injury. Although other studies have shown associations between underlying vascular pathology and neurodegeneration, the effects of air pollution on the brain have been studied in a limited manner thus far. We propose to investigate associations between air pollution exposure, cognitive decline and risk of dementia, and MRI-detected brain abnormalities in the Cardiovascular Health Study (CHS), a large, NHLBI-funded longitudinal study of coronary heart disease and stroke in older adults. This proposal takes advantage of the unique population-based phenotypic resource of brain MRI and cognitive assessment in CHS. In collaboration with an existing CHS ancillary study on air pollution and risk of cardiovascular disease, we will expand upon estimates of exposure to air pollutants produced by vehicle emissions to evaluate the relationship between air pollution and neurological outcomes. Outcomes will include cognitive performance, prevalent and incident dementia (both Alzheimer's disease and vascular dementia), presence of MRI-detected brain abnormalities including brain infarcts and white matter disease, and changes in these measures over time. Drawing on investigator expertise in cognitive function and dementia, brain MRI findings, and the health effects of air pollution, the proposed project provides a unique opportunity to examine air pollution effects on the brain. PUBLIC HEALTH RELEVANCE: The prevalence of cognitive decline and dementia in the elderly is extremely high. Research suggests that environmental factors may play a role in the development of disease;however, little work has examined the potential contribution of air pollution, and particularly traffic-related air pollutants, to neurodegeneration. This study will combine investigator expertise in exposure modeling with a uniquely rich database of longitudinally measured neurological outcomes, to examine the effects of air pollution on the brain in a large, geographically diverse population of older adults. This research is highly significant in light of the pervasiveness of air pollution exposure, its demonstrated links to cardiovascular morbidity and mortality, and the recognized associations between underlying vascular disease and cognitive decline and dementia.